A four-year-old, captive-bred, female Plains garter snake (Thamnophis sirtalis radix) was presented with a large midbody distension (5 cm × 3 cm × 3 cm) in the second third of the body length (total body length 123 cm). Contrast radiography technique excluded an envolvement of the oesophagus or stomach. Aspiration of 8 ml of acellular straw coloured fluid negative for presence of bacteria, fungi or parasites, reduced the swelling to a third of its original size. Surgical exploration revealed a pathologically changed central part of the liver with multiple different sized cysts. Histopathologically the diagnosis was defined as biliary cystadenoma. As the liver had a physiological appearance cranial and caudal to the central area, a partial hepatectomy was performed. The snake recovered well and started to feed spontaneously two days after surgery. During the check up two, four and seven months after hepatectomy, the snake was active and in a good condition. Hypoproteinaemia and altered activity of lactate dehydrogenase were present two months after surgery, azurophilia and hyperuricaemia were present in the blood sampled four months after hepatectomy. Except for azurophilia, the other values of the blood profile were within the expected range for a healthy snake seven months after surgery, indicating full recovery. This is the first detailed report of a successful central resection of a large pathologically changed part of the liver in snakes which was diagnosed as biliary cystadenoma.